title: Urinary cystatin C as a biomarker for acute kidney injury and its immunohistochemical localization in kidney in the CDDP-treated rats.
abstract: Cystatin C, a cysteine protease inhibitor, is a novel biomarker of renal damage. In the present study, we examined the urinary and plasma levels of cystatin C and how useful they are for the early detection of acute kidney injury (AKI) in CDDP-treated rats in comparison with other biomarkers (β2-microglobulin, calbindin, clusterin, EGF, GST-α, GST-μ, KIM-1, NGAL, osteopontin, TIMP-1, and VEGF). The urinary levels of cystatin C, GST-α, KIM-1, and EGF changed prior to proximal tubule damage and increases in plasma urea nitrogen and creatinine levels, suggesting their usefulness for predicting AKI. On the other hand, the plasma cystatin C level hardly changed. We also investigated the localization of cystatin C in the kidney according to the progression of renal damage. Cystatin C was predominantly localized in the proximal tubule of the cortex, and its immunohistochemical expression was not affected by CDDP treatment. In addition, cystatin C was observed in the lumen of the renal tubule in the cortex, cortico-medullary junction, and medulla during the progression of renal damage, although its immunoreactive area ratio was very low. In conclusion, urinary cystatin C measurements can detect CDDP-induced AKI as early as KIM-1, GST-α, and EGF in rats, although the change ratio of the cystatin C was smaller than others. Immunohistochemical cystatin C expression in the proximal tubule of the kidney was hardly changed by the CDDP treatment, but it was newly observed in the renal tubule lumen after CDDP treatment.
authors.affiliation: Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Togashi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Sakaguchi
authors.forename: Mari
authors.initials: M
authors.lastname: Miyamoto
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyamoto
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000473:pathology / Q000652:urine*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism / Q000652:urine; D002945:Cisplatin / Q000633:toxicity*; D055316:Cystatin C / Q000097:blood / Q000378:metabolism / Q000652:urine*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; C525032:Cst3 protein, rat; D055316:Cystatin C; D002945:Cisplatin